Inhibitory effects of sevoflurane on pacemaking activity of sinoatrial node cells in guinea-pig heart
Inhibitory effects of sevoflurane on pacemaking activity of sinoatrial node cells in guinea-pig heart
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DOI：
10.1111/j.1476-5381.2012.01914.x
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发表时间：
2012-08-01
影响因子：
7.3
通讯作者：
Nosaka, Shuichi
中科院分区：
文献类型：
--
作者：
Kojima, Akiko;Kitagawa, Hirotoshi;Nosaka, Shuichi
背景和目的挥发性麻醉剂七氟烷在临床环境中影响心率。本研究探讨了七氟醚对窦房结自律性的影响及其潜在的离子机制。实验方法采用穿孔和常规的全细胞膜片钳技术，在离体豚鼠窦房结细胞中记录自发动作电位和起搏的四种基本离子电流，即超极化激活的阳离子电流（If）、T型和L型Ca 2+电流（分别为伊卡，T和伊卡，L）和缓慢激活的延迟整流K+电流（IKs）。在Langendorff模式下离体记录豚鼠的心率，并在七氟烷吸入期间在体内记录心率。关键结果在分离的SA结细胞中，七氟烷（0.120.71 mM）以定性相似的浓度依赖性方式降低自发动作电位的放电率及其电基础，舒张期去极化率。七氟烷（0.44 mM）使自发放电率降低约25%，并使If、伊卡、T、伊卡、L和IKs分别降低14.4、31.3、30.3和37.1%，而不显著影响电流激活的电压依赖性。通过计算机模拟窦房结细胞电生理，部分再现了七氟醚的负性变时作用。七氟烷降低Langendorff灌注心脏的心率，但在豚鼠体内吸入七氟烷期间不降低心率。结论和意义临床相关浓度的七氟烷减缓了舒张期去极化，从而降低了SA结细胞的起搏活性，这至少部分是由于其对If，伊卡，T和伊卡，L的抑制作用。这些发现为临床环境中七氟烷麻醉期间心率变化提供了重要的电生理学基础。
BACKGROUND AND PURPOSE The volatile anaesthetic sevoflurane affects heart rate in clinical settings. The present study investigated the effect of sevoflurane on sinoatrial (SA) node automaticity and its underlying ionic mechanisms. EXPERIMENTAL APPROACH Spontaneous action potentials and four ionic currents fundamental for pacemaking, namely, the hyperpolarization-activated cation current (If), T-type and L-type Ca2+ currents (ICa,T and ICa,L, respectively), and slowly activating delayed rectifier K+ current (IKs), were recorded in isolated guinea-pig SA node cells using perforated and conventional whole-cell patch-clamp techniques. Heart rate in guinea-pigs was recorded ex vivo in Langendorff mode and in vivo during sevoflurane inhalation. KEY RESULTS In isolated SA node cells, sevoflurane (0.120.71 mM) reduced the firing rate of spontaneous action potentials and its electrical basis, diastolic depolarization rate, in a qualitatively similar concentration-dependent manner. Sevoflurane (0.44 mM) reduced spontaneous firing rate by approximately 25% and decreased If, ICa,T, ICa,L and IKs by 14.4, 31.3, 30.3 and 37.1%, respectively, without significantly affecting voltage dependence of current activation. The negative chronotropic effect of sevoflurane was partly reproduced by a computer simulation of SA node cell electrophysiology. Sevoflurane reduced heart rate in Langendorff-perfused hearts, but not in vivo during sevoflurane inhalation in guinea-pigs. CONCLUSIONS AND IMPLICATIONS Sevoflurane at clinically relevant concentrations slowed diastolic depolarization and thereby reduced pacemaking activity in SA node cells, at least partly due to its inhibitory effect on If, ICa,T and ICa,L. These findings provide an important electrophysiological basis of alterations in heart rate during sevoflurane anaesthesia in clinical settings.